Advances in the physiology, neurobiology, and molecular biology of thermoreception in animal models have outpaced research on human thermoreception. The present continuing project seeks to incorporate this new knowledge into psychophysical studies that test hypotheses about basic mechanisms of human temperature sensitivity. Previous research on the project uncovered evidence of an extensive overlap in sensitivity between the classically defined senses of warmth and cold and the sense of pain, and of interactions between touch and temperature that modify the qualitative and quantitative dimensions of temperature perception. The proposed research builds on these and other more recent findings to investigate how nonpainful temperatures are sensed via multisensory interactions among the cutaneous sensory systems. Specifically, Aim 1 will investigate the parameters of tactile stimulation that underlie the ability of simple contact to suppress thermal sensitivity, particularly nociceptive sensations perceived at innocuous temperatures. Of interest is whether this suppression arises from a general inhibitory action of touch on pain or from a specialized mechanism that attenuates sensitivity to contact thermal stimulation. Aim 2 will test hypotheses about the involvement of recently discovered transient receptor potential (TRP) channels in nonpainful perception of cold and heat using topical application of chemical agents that have been shown to modulate these channels. Aim 3 will test a model of how low-threshold thermal afferent fibers may converge and interact with thermal and nociceptive neurons in the spinothalamic tract. Tests of the model, which is based in part on psychophysical evidence that afferent fibers with sensitivities in the range of warm fibers and cold fibers can relay stimulation to the pain pathway, will provide basic information about the mechanisms of nonpainful heat perception. Aim 4 will determine the relationship of local temperature sensitivity to whole-body temperature perception. Emphasis will be placed on whether local sensitivity is predictive of whole-body sensitivity and on the relationship between the perceived intensity and pleasantness of thermal stimulation. Both of these lines of research will provide missing data on how cutaneous thermal sensitivity contributes to the vital homeostatic function of behavioral thermoregulation. In addition, by testing new hypotheses about the relationship of temperature sensitivity to pain, the proposed research has the potential to provide important new insights into how mild temperatures trigger neuropathic pain in clinical disorders such as fibromyalgia, multiple sclerosis, and stroke.